1. Field of the Invention
This invention relates to methods for improving the yields of polyketide products that are unstable under standard fermentation conditions.
2. Description of Related Art
A large variety of polyketides are produced by fermentation. While many of these polyketides are of medical significance per se, they can also serve as starting materials for the chemical synthesis of medicinally important compounds. For example, Santi et al., WO 02/12534 A2 (2002), incorporated herein by reference, discloses the preparation and use of triketide lactones as precursors of complex natural products such as the anti-cancer agents discodermolide and epothilone. The preparation of triketide lactones by fermentation also has been described in Khosla et al., U.S. Pat. No. 5,712,146 (1998) and U.S. Pat. No. 6,080,555 (2000); Cortes et al., Science 268: 1487–1489 (1995); and Ranganathan et al., Chem. Biol. 6:731–741 (1999).
We have discovered that triketide lactones are unstable under the typical fermentation conditions used for small molecule production, leading to reduced yields of triketide lactones. This invention provides a fermentation method whereby the stability of triketide lactones is increased, thus providing a more economical method for their production.